The influenza A virus is a well characterized virus that infects humans as well as a large number of other species. See, e.g., U.S. Patent Publication No. 20050186621. All of the sixteen (Knossow M and Skehel J. J. (2006) Immunology 119(1):1-7) subtypes of influenza A virus circulate in wild birds and domestic avian species. Few influenza subtypes are epidemic among humans, but periodically pandemic strains derived from animals or birds unpredictably emerge causing wide spread disease of high morbidity and mortality.
Currently, influenza vaccines are produced in fertilized chicken eggs. Eleven days after fertilization, a single strain of influenza virus is injected into the eggs. The virus multiplies in the infected embryo and after several days of incubation, the eggs are opened the virus harvested, purified, chemically inactivated for killed vaccine) and combined with other similarly produced strains to generate an influenza vaccine. On average, one to two eggs are needed to produce one dose of vaccine and the entire production process lasts at least six months.
Traditional influenza vaccines are trivalent in that they contain antigenic proteins from three, different influenza virus strains (e.g., two subtypes A and one subtype B). Accordingly, each antigenically distinct virus must be produced separately in embryonated eggs or tissue culture, isolated and then combined in the final vaccine formulation meaning that one hundred million doses of vaccine necessitate the use of one hundred million eggs to produce only one of the vaccine components. The production of the three virus components currently included in the vaccine requires the use of three hundred million eggs or has similar production requirements in a tissue culture production process. Given the long and costly production protocols, it is unlikely that egg-based production of flu vaccines could be used to contain a flu pandemic.
Therefore, there remains a need for polyvalent influenza compositions and methods that prevent and/or treat infection with the various highly virulent and transmissible influenza strains.